Glean­ings – Genome Syn­the­sized by Sci­en­tists. So What?

It gives us plea­sure to host the trans­la­tion of an ar­ti­cle by Miguel Vi­cente that ap­peared in the Span­ish blog, Esos Pe­queños Bi­chi­tos.

by Miguel Vi­cente

It's in the news! The genome of My­coplasma gen­i­tal­ium has been syn­the­sized! Once again, Craig Venter's group makes head­lines. The ex­cite­ment re­minds me of a sim­i­lar oc­ca­sion – the day al­most eleven years ago when the ex­is­tence of Dolly, the first cloned sheep, was made pub­lic. Re­sults like this trig­ger a va­ri­ety of re­sponses, es­pe­cially in the realm of pub­lic opin­ion.

Ar­ti­fi­cial or syn­thetic?  First, we should at­tempt to de­fine the true na­ture of the re­ported accom­plishment.

Is it, or is it not, an ar­ti­fi­cial genome? If we de­fine ar­ti­fi­cial as some­thing made by hu­mans, the an­swer is yes; on the other hand, if ar­ti­fi­cial means some­thing not present in na­ture, then we en­ter into a murky de­bate. What Venter's team made is the genome from a nat­ural or­gan­ism into which they have in­serted a few pieces from other sources. To avoid con­fu­sion, we might call it a "syn­thetic" genome.

The cen­tral panel of Hiero­nymus Bosch's 'The Gar­den of Earthly De­lights'. Prado Mu­seum, Madrid, Spain. A high-res­o­lu­tion ver­sion of this im­age is avail­able here in Wikipedia (222.86 MB).

Next, we should ex­plain that, for the time be­ing, this syn­thetic genome is not to be found in­side its par­ent micro­organism, My­coplasma gen­i­tal­ium, but in­side a yeast cell, in­stead. In con­se­quence, it con­tains some added seg­ments to al­low its prop­a­ga­tion in the new host cell. Thus, we could clar­ify by call­ing it a chimera or a "hy­brid" ge­nome.

It is not yet known for cer­tain whether a hy­brid syn­thetic genome can be main­tained in­side a cell sim­i­lar to its par­ent with­out caus­ing trou­ble. Ex­pe­ri­ence shows that intro­duced changes, even mi­nor ones, are apt to un­bal­ance the re­cip­i­ent mi­crobes, mak­ing them less ef­fi­cient. More­over, tech­niques do not seem to be avail­able to re­move those DNA seg­ments that are alien to My­coplasma from the syn­thetic hy­brid genome with­out dis­rupt­ing the in­tegrity of the rest. Note that the larger the DNA mol­e­cule, the more dif­fi­cult to ma­nip­u­late it.

Yeast as coworker.  Ac­tu­ally, the sci­en­tists were un­able to as­sem­ble DNA se­quences con­tain­ing half of the My­coplasma genome in the "test tube". Even the as­sem­bly of half genomes in E. coli, a mi­crobe more amenable to gene ma­nip­u­la­tion than My­coplasma, failed. In con­se­quence, the full genome was as­sem­bled in­side yeast cells. Thus, the genome has not been syn­the­sized ex­clu­sively in the test tube; the ma­chin­ery used by yeast to man­age its own genome came to the res­cue. Ad­ditionally, for safety, one of the My­coplasma gen­i­tal­ium vir­u­lence genes was in­ac­ti­vated.

Nev­er­the­less, the tech­ni­cal ad­vances achieved by these re­searchers and em­ployed for the assem­bly of this syn­thetic hy­brid quasi genome are un­ques­tion­able. It is rea­son­able to ex­pect that fu­ture im­prove­ments will en­able the team to pro­duce a genome iden­ti­cal to the orig­i­nal.

Count­less ben­e­fits and un­fore­seen evils.  Does this news mean, as head­lines im­ply, that we are cre­at­ing ar­ti­fi­cial life? My an­swer is no. Even if all the present short­com­ings are re­solved, the re­sult will still be a copy of an ex­ist­ing genome. To in­vent any­thing dif­fer­ent, it would be necessar­y – in my view – to deeply un­der­stand the role of each in­di­vid­ual gene within the full set of genes in a cell, as well as all of their in­ter­ac­tions. More­over, the in­ven­tions may not prove to be bet­ter or more ef­fi­cient than the nat­u­rally avail­able items. This is not pes­simism. Bac­te­ria have al­ready been test­ing all the pos­si­ble ways to mod­ify their genomes for 3.5 bil­lion years. Since their intel­ligence is, if not higher than, at least more ef­fi­cient than that of hu­mans, it would be sur­pris­ing if we can im­prove on them. Un­doubt­edly, it is fea­si­ble to ob­tain genomes tai­lored to thrive in speci­fic en­vi­ron­ments. While some will serve to rem­edy the predica­ments of hu­mankind, oth­ers will only worsen them.

Bac­te­ria al­ready in­vented it.  The use­ful­ness of such "in­ven­tions" will of ne­ces­sity de­pend on a know­ledge of how genes func­tion in var­i­ous ge­netic and en­vi­ron­men­tal back­grounds, a know­ledge that in my opin­ion we still do not have in suf­fi­cient depth. Re­search fund­ing has failed to tar­get this as a pri­or­ity. In ad­di­tion to the head­start that bac­te­ria have in this quest, there are other caveats. Pro­teins, the mol­e­cules that sup­port the chem­istry of life in­side cells, can only adopt a lim­ited num­ber of struc­tures for each given chem­i­cal func­tion. Fur­ther­more, bio­di­ver­sity, and there­fore adap­ta­tion to the en­vi­ron­ment, is not only a func­tion of the in­di­vid­ual bio­chem­i­cal re­ac­tions, but also of the global pat­terns of cell reg­u­la­tion. Reg­u­la­tory mech­a­nisms evolve by dif­ferent path­ways than do in­di­vid­ual pro­teins, and they also in­volve the added com­plex­ity of pro­tein-pro­tein in­ter­ac­tions. We are knee-deep in ig­no­rance re­gard­ing these mech­a­nisms.